Boosting PD-1 Blockade's Efficacy in CRC: The Role of Stabilized TFF2-CTP

The abstract discusses the limited effectiveness of immune checkpoint blockade in colorectal cancer (CRC), with benefits primarily observed in microsatellite unstable tumors. It highlights that PD-L1 expression is generally associated with poor prognosis in CRC but is linked to improved outcomes with PD-1 blockade. The study investigates the role of PD-L1 in CRC development and explores the potential of targeting myeloid-derived suppressor cells (MDSCs) alongside PD-1 inhibition in mouse models.

Researchers created mice with conditional expression of the murine Pdl1 gene and induced CRC using azoxymethane and dextran sodium sulfate. They observed accelerated tumor growth and increased myeloid cells, particularly MDSCs, in these mice. There was also a reduction in CD8+ T cell infiltration and anti-tumor immunity.

Trefoil factor 2 (TFF2), an anti-inflammatory peptide, was found to inhibit tumor growth by curbing MDSC expansion. A modified version of TFF2, fused with additional peptides, was shown to be effective in circulation and retained its bioactivity. When combined with anti-PD-1 treatment, it significantly reduced tumor growth and increased the presence of tumor-infiltrating CD8+ T cells while decreasing regulatory T cells and MDSCs.

The study suggests that TFF2 could enhance the efficacy of PD-1 blockade in CRC by suppressing MDSC expansion, indicating the potential of TFF2-CTP in combination immuno-oncology treatment. Further testing of the combined therapy is ongoing in a specific mouse model.

Citation: Woosook Kim et al., "Stabilized recombinant trefoil factor 2 (TFF2-CTP) enhances anti-tumor activity of PD-1 blockade in mouse models of colorectal cancer," Proceedings of the Annual Meeting of the American Association for Cancer Research 2020, Philadelphia, PA: AACR, Cancer Res 2020;80(16 Suppl):Abstract nr 6640.